DESCRIPTION: The fundamental goal of this project is to understand mechanisms whereby early life experiences profoundly influence mechanisms of ventilatory control in adult mammals (i.e. developmental plasticity). In the first three years of this project, it was demonstrated that the ventilatory control system is subject to developmental plasticity in the hypoxic ventilatory response. Specifically, one month of perinatal hyperoxia (60 percent) causes a persistent attenuation of the hypoxic ventilatory response in adult rats, two to four months after the hyperoxic exposure had ended. Since similar effects are not observed in rats exposed to the same duration and level of hyperoxia as adults, this functional impairment is unique to development. The aims of this proposal for competitive renewal are to extend these observations by testing the following hypotheses: 1) that perinatal hyperoxia causes persistent functional impairment of the hypoxic ventilatory response only within a limited developmental "window," approximately two weeks in length; 2) that slow, partial functional recovery occurs spontaneously with advancing age; and 3) that functional recovery of the hypoxic ventilatory response can be induced by sustained exposure to hypoxia, either within the developmental window or after the developmental window has expired. Experiments will combine neurophysiological recordings of hypoxic phrenic and carotid chemoafferent responses in anesthetized rats with measurements of the hypoxic ventilatory response in awake rats. These studies may have important clinical implications for infants subjected to oxygen therapy during critical care; they may suffer impaired chemoreflexes throughout their lives if excessive arterial oxygenation occurs during the developmental window. Further understanding of mechanism(s) that underlie developmental plasticity with its associated functional impairments may provide the rationale for therapeutic intervention, thereby enhancing functional recovery.